Blood schizontocidal and gametocytocidal activity of 3-hydroxy-N'-arylidenepropanehydrazonamides

Leven, Michael and Held, Jana and Duffy, Sandra and Tschan, Serena and Sax, Sibylle and Kamber, Jolanda and Frank, Walter and Kuna, Krystina and Geffken, Detlef and Siethoff, Christoph and Barth, Stéphane and Avery, Vicky M. and Wittlin, Sergio and Mordmüller, Benjamin and Kurz, Thomas. (2014) Blood schizontocidal and gametocytocidal activity of 3-hydroxy-N'-arylidenepropanehydrazonamides. Journal of medicinal chemistry, 57 (19). pp. 7971-7976.

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Official URL: http://edoc.unibas.ch/dok/A6319191

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3-Hydroxy-N'-arylidenepropanehydrazonamides represent a new class of antiplasmodial compounds. The two most active phenanthrene-based derivatives showed potent in vitro antiplasmodial activity against the 3D7 (sensitive) and Dd2 (multidrug-resistant) strains of Plasmodium falciparum with nanomolar IC50 values in the range of 8-28 nM. Further studies revealed that the most promising derivative, bearing a 4-fluorobenzylidene moiety, demonstrated in vivo antiplasmodial activity after oral administration in a P. berghei malaria model, although no complete parasite elimination was achieved with a four-dose regimen. The in vivo efficacy correlated well with the plasma concentration levels, and no acute toxicity symptoms (e.g., death or changes in general behavior or physiological activities) were observed, which is in agreement with a <1000-fold lower activity against L6 cells, a primary cell line derived from mammalian (rat) skeletal myoblasts. This indicates that lead compound 29 displays selective activity against P. falciparum. Moreover, both phenanthrene-based derivatives were active against stage IV/V gametocytes of P. falciparum in vitro.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Parasite Chemotherapy (Mäser)
UniBasel Contributors:Wittlin, Sergio
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Chemical Society
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:20 Oct 2017 06:30
Deposited On:09 Jan 2015 09:24

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